Antidepressant prescribing in the precision medicine era: a prescriber’s primer on pharmacogenetic tools

Abstract

About half of people who take antidepressants do not respond and many experience adverse effects. These detrimental outcomes are in part a result of the impact of an individual’s genetic profile on pharmacokinetics and pharmcodynamics. If known and made available to clinicians, this could improve decision-making and antidepressant therapy outcomes. This has spurred the development of numerous pharmacogenetic-based decision support tools. In this article, we provide an overview of pharmacogenetic decision support tools, with particular focus on tools relevant to antidepressants. We briefly describe the evolution and current state of antidepressant pharmacogenetic decision support tools in clinical practice, followed by the evidence-base for their use. Finally, we present a series of considerations for clinicians contemplating use of these tools and discuss the future of antidepressant pharmacogenetic decision support tools.

Roadmap for Routine Pharmacogenetic Testing in a Psychiatric University Hospital

“…Actually, expert panels have started to publish dosing guidelines for several antidepressants, especially tricyclic antidepressants, when the genotypes of CYP450 enzymes are available [24,26,27]. Meanwhile, many commercial pharmacogenetic-based decision-support tools are available in psychiatry that analyze a limited number of genetic variants and use certain undisclosed algorithms promise to predict the treatment outcome and ADRs [28,29]. They are supposed to provide information relevant for the selection of an antidepressant and for decisions on dosing; additionally, they may flag potential drug-drug interactions [28,29].…”

“…Meanwhile, many commercial pharmacogenetic-based decision-support tools are available in psychiatry that analyze a limited number of genetic variants and use certain undisclosed algorithms promise to predict the treatment outcome and ADRs [28,29]. They are supposed to provide information relevant for the selection of an antidepressant and for decisions on dosing; additionally, they may flag potential drug-drug interactions [28,29]. Although there are some promising data on treatment guided by pharmacogenetic tools being superior over standard treatment [30], data of adequately powered randomized controlled trials is still insufficient to support widespread use [18,31].…”

Depression-inducing drugs and the frequency of depression in Alzheimer’s disease and APOE ε4 carriers

“…Approximately half of the people placed on an antidepressant medication do not show signs of improvement and over half will experience an adverse side effect. This is partly due to each person's genetic makeup and its impact on the PK and PD of the medication 56 . Many pharmacogenomic studies have been conducted on antidepressant medications and found that their efficacy is highly correlated with SNP variations.…”

Deuterium‐substituted 2‐(2′‐((dimethylamino)methyl)‐4′‐[18F](fluoropropoxy)phenylthio)benzenamine as a serotonin transporter imaging agent

“…In the past few decades, many selective serotonin reuptake inhibitors, SSRIs, such as fluoxetine, sertraline, paroxetine, and escitalopram, specifically target serotonin transporter (SERT) and inhibit serotonin reuptake to the neurons. Consequently, SSRIs are useful in the treatment of depression as well as many other psychiatric conditions by regulating the serotonin concentration in the synapse . Positron emission tomography (PET) imaging for SERT binding sites in the brain with [ 11 C]DASB ( T 1/2 = 20 min) (Figure 2) has been reported, and its clinical application is well reported in the literature .…”